This is the second competitive renewal application for the University of Colorado Health Science Center (UCHSC) MSTP training grant, which currently has 14 slots. The goal of this MST Program is to train outstanding physician-scientists who will become the future leaders in their chosen discipline of study. To accomplish this goal, we select UCHSC MSTP students from a national applicant pool, specifically seeking out those candidates whose record of research, academic, and leadership achievements are exemplary. The selected MSTP students enter a flexible, yet highly rigorous training program that fully integrates graduate and medical school course work in the first two years, typically entails 3-4 years of thesis work, and is completed with 15-24 months of clinical work. Thus, the requirements for both the Ph.D. and M.D. degrees are met in about a 7- to 8-year timeframe. To enhance the potential success of our MSTP students, we provide career guidance extending beyond the Ph.D. thesis years, thus placing our graduates in the very best residencies and fellowships. The students choose from 118 training faculty in 14 graduate training programs that are primarily interdepartmental in nature, located at three sites: the UCHSC, National Jewish Medical Research Center (NJMRC), and the University of Colorado at Boulder (CU-Boulder). These three training sites are nationally prominent as institutions of research and clinical superiority, with a combined extramural support of greater than $500 million. We currently have 42 total students (33% women and 14% URM) and we recruit 6 students per year. Since 1983, 80 students (31% women and 10% URM) have been associated with the Program, with 33 completing both degrees in 7.8 years, and only 6 (7.5%) students leaving the Program; the past 5 years we have generated a record of success in recruiting outstanding candidates, and more recently we have also recruited qualified minority applicants. However, the number of training faculty, total and minority applicants, and training programs of the UCHSC MST Program has increased remarkably since the last submission, and an increasing number of applicants wish to matriculate in our Program. Thus, in this coming grant period, we request 20 total positions by Year 5, increasing from the current total of 10 by 2 positions per year. This increase will allow us: (1) to realize our full potential as a premier MSTP training site, servicing not only the Rocky Mountain/Southeastern region, but also the entire country; and (2) to continue building a legacy of training outstanding biomedical scholars. [unreadable] [unreadable]